Solutions

UNIT IV

SOLUTIONS

V.MANIMARAN LECTURER DEPARTMENT OF PHARMACEUTICS SRM COLLEGE OF PHARMACY

Solutions

‐ In physicochemical terms, solutions may be  prepared from any combination of solid, liquid or  gas, the three states of matter ‐ Liquid preparations that contain one or more   soluble chemical substances dissolved in a suitable  solvent or mixture of mutually miscible solvents ‐Homogenous mixture that is prepared by dissolving  a solid, liquid or gas in another liquid and represents  a group of preparations in which the molecules of  the solute or dissolved substance are dispersed.

Types of Solutions 1. Solid Solution – the solvent is solid a. Solid in solid Example: Cu + gold= 12 karat yellow gold b. Liquid in solid Example: Hg dissolved in Ag = amalgam c. Gas in solid Example: air dissolved in soap = floating soap 2. Liquid Solution – the solvent is liquid a. solid in liquid Ex: salt in water b. Liquid in liquid Ex: alcohol and water c. Gases in liquid Ex: carbonated beverages

3. Gaseous Solutions – the solvent is gas a. Solid in gas Example: sulfur in air b. Liquid in gas Example: water vapor in air c. Gas in gas Example: oxygenated air

Factors affecting the “rate” of solubility 1.  Particle size – an increase in surface area to the solvent  will increase rate of solution. So the particle size should  be reduced by comminution before it is dissolved. 2.  Agitation – increases the rate of solution by removing  from the surface of the solute. The more concentrated  solution around it the less concentrated the solvent.

3. Temperature heating a liquid also causes solution to take place more  rapidly by increasing the frequency which solvent  molecules collide with the surface of the dissolving  mixture

Factors Affecting Solubility of Solute 1.  Temperature Endothermic reaction – The process of solution  where heat is applied and absorption of the heat  takes place in the solutes, this increase in  temperature will cause more of the solute to go  into solution.

Exothermic reaction – solute gives off heat during  the process of solution; solubility is decreased with  an increase in temperature. Example: more soluble in cold than hot water Methyl cellulose and calcium salts such as Ca(OH)2  2. Molecular Structure The general rule: “like dissolves like” 3. Effects of other substance Example: Iodine is very slightly soluble in water but  when added to a concentrated solution of KI dissolves  immediately. 4. pH – Many of the organic substances which are used  medicinally are either weak acids or weak bases. And  their aqueous solubility depend upon the pH of the  solvent.

Examples of Weak  Bases • Alkaloids – atropine,codeine,  morphine • Antihistamines – diphenhydramine,  tripelennamine • Local anesthetics – cocaine, procaine,  tetracaine

Examples of Weak  Acids • Barbiturates – phenobarbital,  pentobarbital • Sulfonamides – sulfadiazine,  sulfacetamide

Water and alcohol Solubilities Of some Selected Weak Acids, Weak Bases, and Their Salts Number of mL of Solvent Required To Dissolve 1 g of Drug Drug

Water

Alcohol

Atropine

455

2

Atropine Sulfate

0.5

5

Codeine

120

2

Codeine Sulfate

30

1,280

Codeine Phosphate

2.5

325

Morphine

5,000

210

Morphine Sulfate

16

565

Phenobarbital

1,000

8

Phenobarbital sodium

1

10

Procaine

200

soluble

Procaine HCl

1

15

Sulfadiazine

13,000

sparingly soluble

Sodium Sulfadiazine

2

Slightly soluble

Relative Terms of Solubility Descriptive Term

Parts of Solvent required

Very Soluble Freely soluble Soluble Sparingly soluble Slightly soluble Very slightly soluble Practically soluble or Insoluble

Less than 1 From 1 to 10 From 10 to 30 From 30 to 100 From 100 to 1000 From 1000 to 10,000 From 10,000 and over

Solubilities Of Selected Organic Compounds in Water as a Demonstration of Chemical Structure-Solubility Relationship

Compound

Number of mL of water Required to Dissolved 1 g of compound

Formula

Benzene

C6H6

1430

Benzoic acid

C6H5COOH

Benzyl Alcohol

C6H5CH2OH

25

Phenol

C6H5OH

15

Pyrocatechol

C6H4(OH)

2

2.3

Pyrogallol

C6H3(OH)

3

1.7

Carbon Tetrachloride

CCl4

Chloroform

CHCl3

Methylene chloride

CH2Cl2

275

2000 200 50

Inorganic Molecules 1.  Monovalent cation and anion of an ionic compound are  generally water soluble Examples: NaCl, LiBr, KI, NH4NO3 2. Only one of the two ions is monovalent – compounds are  water soluble Examples: BaCl2, MgI2, Na2SO4, Na3 PO4 3. Both ions are multivalent ‐ poor water soluble. Examples: CaSO4, BaSO4, BiPO4 Exceptions: ZnSO4 and FeSO4 4. Common salts of alkali metals are usually water soluble Exception: Li2CO3

5. NH4 and quaternary NH4 salts are water soluble 6. Nitrates, Nitrites, acetates, chlorates and  lactates are  generally water soluble Exceptions: silver and mercurous acetate 7. Sulfates, sulfites and thiosulfates are generally water soluble Exceptions: Calcium and Barium salts 8. Chlorides, bromides and iodides are water soluble Exceptions: salts of silver and mercurous ions 9. Acid salts corresponding to an insoluble salt will be more  water soluble than organic salts. 10. Hydroxides and oxides of compounds other than alkali  metal cations and the  ammonium ion are generally water  insoluble.

11. Sulfides are water insoluble except for their alkali  metal salts 12. Phosphates, carbonates, silicates, borates and  hypochlorites are water insoluble except for their alkali  metal salts and ammonium salts

Organic Molecules 1.  Molecules having 1 polar functional group – soluble  to the the total lengths of 5C’s 2.  Molecules having branched chains are more soluble  than the corresponding straight‐chain compound. 3.  Water solubility decreases with increase in MW 4.  Increased structural similarity between solute and  solvents accompanied by increase solubility.

Solvents for Liquid Preparations 1.  Water – has the widest range of usefulness of all the  solvents employed in pharmaceutical dispensing or  manufacturing. It is a good solvent for most  inorganic and organic  2.  Alcohol USP, Ethyl Alcohol, Ethanol – good solvent for  many organic substances both natural and synthetic.  Is 94.9 to 96.0% alcohol at 15.560C. Limit: 0.5% = 6 to 12 years, 5% = over 12, 10% =  adult 3. Dehydrated Alcohol – 99.5% absolute alcohol is  partially free from water.

4. Diluted Alcohol NF‐ prepared by mixing equal volume of  Alcohol USP and purified water. 5. Alcohol, Rubbing – contains about 70% of ethyl alcohol by  volume the remainder consists of water, denaturants with  or without color additives and perfume oils and stabilizers. 6. Glycerin USP ( Glycerol) – clear syrupy liquid with sweet  taste. It is miscible both with water and alcohol. Excellent  solvent for tannins, phenol and boric acid. It has a  preservative qualities. 7. Propylene Glycol – miscible in water, acetone, alcohol and  chloroform 8. Polyethylene glycol 400 – miscible in water, acetone alcohol  and other glycols 9. Chloroform – miscible with alcohol, ether, benzene, hexane  and both fixed and volatile oils 10. Acetone – miscible with water, alcohol, ether, chloroform  and most of the volatile oils.

Methods of Preparing Solutions 1.  Simple Solution – prepared by dissolving the  solute in the solvent Examples: Calcium hydroxide solution USP  (lime water), Sodium Phosphate solution and  Strong Iodine solution USP (lugol’s) 2. Solution by Chemical reaction – prepared by  reacting two or more solutes with each other in  a suitable solvent. Examples: Aluminum subacetate – prepared by  reacting aluminum sulfate sol. with calcium  carbonate and acetic acid forming magma.

Magnesium Citrate = prepared by reacting official  magnesium carbonate with citric acid, flavoring and  sweetening agents, filtering talc and carbonating it by  potassium or sodium bicarbonate.  Use: Saline cathartic Sodium Citrate and Citric acid oral solution = contains 100  mg sodium citrate and 67 mg citric acid in each ml od  aqueous solution. Use: Systemic alkalinizer

3.  Solution by Extraction – vegetables or animal  origin are often extracted with suitable solvent.   Preparation of this type may be classified as solutions  but more often EXTRACTIVES 

Common Methods of Expressing the Strengths  Of Pharmaceutical Preparations Percent weight in volume ‐ number of grams of a  constituents in 100mL of preparation (1% w/v = 1g of constituent in 100mL of preparation) Percent volume in volume ‐ number of mL of  constituent in 100mL of preparation (1%v/v 1 mL of constituent in 100mL of preparation) Percent weight in weight ‐ no. of grams of a constituent  in 100g of preparation (1%w/w = 1g of constituent in 100g of preparation)

Common Methods of Expressing the Strengths  Of Pharmaceutical Preparations Ratio strength weigh in volume ‐ w/v no. of grams of  constituent in stated no. of mL of preparation (1:1000w/v = 1g of constituent in 1000mL of  preparation) Ratio strength volume in volume – v/v no. of mL of  constituent in stated number of mL of preparation (1:1000 v/v = 1mL of constituent in 1000mL preparation) Ratio strength weight in weight – w/w number of grams of  constituent in stated number of grams of preparation (1:1000 w/w = 1g of constituent in 1000g of  preparation)

Examples of Oral Solution by Category 1.  Antidepressants Notriptylline HCl – Pamelor Oral Solution Fluoxetine HCl – Prozac Liquid 2. Antiperistaltic Diphennoxylate HCl and Atropine Sulfate‐ Lomotil Liquid Loperamide HCl‐ Immodium A‐D Liquid 3. Bronchidilator Theophylline – Theophylline Oral Solution 4. Antipsychotics Haloperidol – Haldol Concentrate Perphenazine – Trilafon Concentrate Thiothixene HCl – Navane Concentrate

5. Cathartics Magnesium citrate  Sodium Phosphate – Phospho‐Soda (fleet) 6. Corticosteroid  Prednisolone Sodium Phosphate‐ Pediapreu Oral Solution 7. Dental Care Protectant Sodium Flouride – Pediaflor Drops 8. Electrolyte Replenisher Potassium Chloride – KaoChlor 10% Liquid 9. Fecal Softener Docusate Sodium‐ Colace syrup

10. Hematinic Ferrous Sulfate ‐ Fer‐in‐sol Drops 11. Histamine hydrogen Antagonist Cimetidine HCl liquid – Tagamet HCl Liquid 12. Narcotic Agonist Analgesic Methadone HCl – Methadone HCl 13. Vitamin D source Ergocalciferol – Calciferol drops

AQUEOUS SOLUTIONS Is one where water is used as a  major ingredient.  Water is used as a vehicle and a solvent for the  desired flavoring or medical agent. CHARACTERISTICS OF WATER 1. Tasteless 2. Freedom from irritating qualities 3. Lack of pharmacologic activity DISADVANTAGES 1. Favorable medium for many chemical reactions 2. Support growth of microorganisms when  contaminated 3. In pure form add cost to production

PREPARATION 1.  Distillation 2.  Demineralization or Deionization 3.  Reverse Osmosis **Demineralization – This ionization process is the well  known Zeolite process of softening water high mineral  content. This resin may be acid or cations exchanger  and base or anion exchanger. • Zeolite – act as a catalyst such as dehydrated aluminum.  Calcium sodium sulfate. * Deionization process do not necessarily produce purified  water which will comply with USPHS ( US Public Health  Service) requirements for drinking water, the water should  be purified before they can used for pharmaceuticals

**Reverse Osmosis – Transport of solvent through  semipermeable membrane separating 2 solutions  of different concentrations (less concentrated  and more concentrated) A reversely new separation process w/c in  principle may be applied to the separation,  concentration and fractionalization of inorganic  or organic substances in aqueous or non‐aqueous  solutions in the liquid or the gaseous phase is  known reverse osmosis. Also referred as “crossflow or tangential flow”  membrane filtration

PORE SIZE 1. Microfiltration (0.1 to 2 microns) = bacteria 2. Ultrafiltration (0.01 to 0.1 microns) = virus 3. Nanofiltration (0.001 to 0.01 microns) =  organic compounds in the MW of 300 to  1000 4. Reverse Osmosis (smaller than 0.001  microns

AROMATIC WATERS Aromatic water is also called medicated water,  defined in the USP as clear, saturated aqueous  solutions of volatile oils or other aromatic or  volatile substances. These are to be free from 1.  Smoke like odor and other odors 2. Must have odor and taste similar to those oil or  drugs from which they are prepared. 2 Components 1. Volatile oil 2. Water

Official Processes of Preparation 1.  Distillation Cohobation – is the process of obtaining aromatic  water by distillation one or more times from  delicate drugs with small quantities of volatile  principles. Examples: Stronger Rose( Aqua Rose Fertier, Triple  Rose Water) 2. Solution Method A. Simple Solution Method Example: Peppermint water  Concentrate Synonyms: Aqua Mint, American Mint Latin name: Aqua Menthae Piperitae

Formula: Peppermint oil 20mL 90%Ethanol 600mL Purified Talc 50g Purified Water q.s.to make 1000mL Uses: Vehicle for internal aqueous sol. Carminative,      flavoring diluent Description: Clear, saturated solution

B. Alternate Solution by Intervention ‐ The volatile material is mixed thoroughly with 15g of  purified talc.  ‐The mixture is agitated with purified water for ten  minutes prior to filtration. ‐ The disadvantage of this method is the fineness of  the filter aid which passes through the filter paper.

AROMATIC WATER Stability Aromatic water are not permanently stable preparations Preservation of Aromatic Water Protect from excessive light and heat. Deterioration may due to  volatilization. Decomposition or mold growth producing cloudy  preparation or disagreeable odor.

Other examples Of water Orange Flower Water, NF Synonyms: Aqua Auranti Florum, Shanger Orange Flower, Triple  Orange Flower water Formula: It is a saturated solution of odoriferous principles  of  flowers of Citrus Aurantum Linne. Uses: A Flavored vehicle and perfume in solutions, syrup and elixirs.

Cinnamon Water Preparation: Cinnamon Water Synonym: Casio Nare, Cassia Oil Latin Name: Aqua Cinnamoni Formula: Cinnamon oil  20mL Ethanol 90% 600mL Purified Talc 50g Purified water q.s. to make 1000mL Procedure: Alternate Solution Method Uses: As flavored vehicle for internal aqueous  solution, antiseptic in eye lotion, carminative Description: Clear, Saturated Solution

AQUEOUS ACIDS Inorganic and organic acids such as HCl,  HNO3, HI, HBr, H2SO4, and Hac., of great  importance in chemical and pharmaceutical  manufacturing Division of inorganic acids 1.  Hydroacids – no oxygen 2.  Oxygen containing acids

Diluted Acetic Acid Synonym: Dilute Acetic acid Latin Name: Acidum Aceticum Dilatum Formula: Acetic Acid Purified water q.s. to make

158mL 1000mL

Uses: Bactericidal and occasionally used in 1% solution  for surgical dressings of the skin; 1% spermatocidal,  as vaginal douche Description: Clear, colorless, having a strong  characteristic odor and sharply acid taste, miscible  with water.

Examples of Official Acids Although Not All of  them are Aqueous acids 1. Acetic Acid

7. Folic Acid

2. Diluted Acetic Acid

8. Citric Acid

3. Glacial Acetic Acid

9. Folic Acid

4. Diluted Hydroiodic Acid

10. Phosphoric Acid

5. Diluted Hydrochloric Acid

11. Tartaric Acid

6. Hypophosphorous Acid

12. Salicylic Acid

GARGLES Are aqueous solutions used for treating the  pharynx and nasopharynx by forcing air from  the lungs through gargle which is held in the  throat. Many gargles must be diluted with  water prior to use.

Gargles Examples: Phenol Gargle and Potassium Chlorate  (also known as Golden Gargle) and Phenol Gargle  are official in B.P.C Preparation: Phenol Gargle Synonym: Phenolic Solution, Carbolic gargle Latin name: Gargarisma Phenol Formula: Contains 50mL of Phenol Glycerin  (16%  w/w phenol and 84% w/w glycerin), 10mL  amaranth solution(1%w/v in chloroform water)  and water to make 1L. This is diluted with warm  water equal volume before use . For external use Uses: antiseptic and soothing effect

WASHES (LAVATIO ORI) A mouthwash is an aqueous solution which is most  often used for its 1.  Deodorant 2.  Refreshing 3.  Antiseptic effect It may contain alcohol, glycerin, synthetic sweeteners,  surface active agent, flavoring and coloring. Commercial preparations contain local anti‐infective  agents: hexetidine and cetylpyridinium chloride.

Examples: 1.  Dobell’s solution or compound Sodium Borate NF  – contains Sodium borate. Liquified Phenol and  Glycerin and sodium Bicarbonate – use: antiseptic 2.  Compound Sodium Chloride Mouthwash – Zinc  sulfate and ZnCl2 Special Washes 1.  Eye washes (Collyrium) ‐ as anesthetic, anti‐ infective, diagnostic, myotic and anti‐ inflammatory 2.  Mouthwash (Collutorium)‐ antibacterial 3.  Nasal wash ( Collunarium) ‐ antibacterial and  antiseptic

JUICES Juices are formerly known as INPISSATED JUICES. A  juice prepared from ripe fruit, aqueous in  character, and it is used in making syrups  employed as vehicle. Examples: Cherry juice and Raspberry juices are  official in USP

SPRAYS • Aqueous solutions in the form of coarse droplets or  as finely divided solids to be applied topically, most  usually to the nasal‐ pharyngeal tract or to skin • Applied to the mucous membrane of the nose and  throat by means  of an atomizer or nebulizer • Such sprays may contain antibiotics, antihistamine,  vasoconstrictor, alcohol and suitable solubilizing and  wetting agents • Another device to deliver spray is called “spray‐o‐ mizer”, this is for throat  Examples: Nasalide(Syntex), Nostrilla

COLLODIONS Are liquid preparation composed by pyroxillin dissolved a solvent mixture. Usually composed of alcohol and ether with or without added substances Pyroxillin (nitrocellulose soluble gun cotton, collodion cotton) is obtained by the action of mixture of nitric acid and sulfuric acids on cotton and consists chiefly of cellulose tetranitrate.

Uses Of Collodion 1. As a protective coating to the skin 2. As medication where a thin layer of the medication is firmly placed against the skin Direction Of Use Collodion are applied to the skin by means of a soft brush or other suitable applicators. The solvent rapidly evaporates, leaving a film residue of pyroxillin.

Example Of Official Collodion 1. Which provides protective coating A. Collodion, USP is a clear or slightly opalescent viscous liquid prepared by dissolving 4% W/V pyroxillin in 3:1 mixture of ether and alcohol. B. Flexible Collodion, USP is prepared by adding 2% of Camphor and 3% castor oil to the Collodion 2. Which provides medication A. Salicylic acid Collodion, USP is 10% solution of salicylic acid in flexible collodion. Used as keratolytic effect ( topical drug that softens the superficial keratin-containing layer of the skin and promotes its desquamation) especially in the removal of corns from the toes Synonym: Corn solvent

SPIRITS

Formerly called “Essences” alcoholic or  hydroalcoholic solutions of volatile  substances. First Spirits 1.  Brandy – Spiritus Vini vitis – 48 to 54% alcohol from  grapes 2.  Whisky ‐ Spiritus frumenti – 47 to 53% of alcohol  from cereals Uses: 1.  As flavoring agents pharmaceutically 2.  For therapeutic value of the aromatic solute  medicinally

Preparation of Spirits 1. Simple Solution Majority of spirits are prepared by dissolving the solute in  alcohol by agitation. Filtration is generally desirable to  obtain a sparking clear product. Example: Aromatic Spirit ‐ 62 to 68% hydroalcoholic solution of  ammonia and ammonium carbonate flavored and perfumed  with lemon, lavender and myristica oil.

2. Solution with Maceration Macerate the vegetable materials in a suitable solvent to  remove the undesired constituents or to extract one which is  desired.

Example: Peppermint Spirit (Spiritus Menthae Piperitae) – 79 to  85% hydroalcoholic solution containing 10% peppermint oil Use: digestive aid or carminative

Preparation of Spirits 3. Solution by Chemical Reaction Only the preparation of Aromatic Spirit of Ammonia NF,  involves a chemical reaction where the official Ammonium  carbonate

4. Distillation No spirits currently official are prepared by  distillation, However, two products of historical  significance which is official in NF are prepared by  distillation. Examples: Brandy and whisky

TOOTHACHE DROPS Are preparations used for the temporary relief of  toothache by application of a small cotton saturated with  the product into the tooth cavity Example: Clove oil and mixture of phenol with camphor or  creosote

DENTAL ORAL SOLUTION A variety of medicinal substances are employed topically in  the oral cavity. Examples: 1.  Benzocaine – Topical anesthetic Indicated for temporary relief  of pain, soreness and irritation in the mouth associated with  teething and others 2.  Caphorated Parachlorophenol – Dental anti‐infective. A  eutectic liquid composed of 65% camphor and 35%  parachlorophenol. Use in the dentistry of the sterilization of  deep root canals.

3. Carbamide Peroxide – Dental anti‐ineffective . Acts as  chemomechanical cleansing and debriding agent through  the release of bubbling oxygen. Commercial product Gly‐ Oxide ‐ contains 10% carbamide in flavored anhydrous  glycerin. 4. Cetylpyridinium Chloride Solution and Lozenges‐ Local  anti‐infective. Commercial counter parts. Cepacol Mouthwash/Gargles and Lozenges 5. Erythrosine Sodium Solution/tablets‐Diagnostic Aid.  Solution applied to the teeth to reveal plaque left by  inadequate brushing. Tablets same purpose and are not to  be swallowed. 6. Eugenol ‐ Dental Analgesic. Applied to dental cavities and  dental protectives

7. Lidocaine Oral Spray – Topical dental anesthetic.  Applied through metered spray in the amount of  10mg per spray. 8. Nystatin Oral Suspension – Antifungal 9.  Na Fluoride /Tablets ‐ Dental carries prophylactic 10.  Saliva Substitutes – contains  electrolytes in  CMC base and indicated for the relief of drymouth and throat in xerostomia 11. Triamcinolone Acetonide Dental Paste – Topical  Anti‐inflammatory 12. Zinc Oxide‐Eugenol Mixtures – A temporary filling  mix

INHALATIONS ‐ drugs or solutions of drugs administered by the nasal or  oral respiratory route. ‐ A widely used instrument capable of producing fine  particles for inhalation therapy is the nebulizers =When volatile medication is added to the water in the  chamber, the medication is volatilizes and also inhaled by  the patient and Humidifiers will be used =The common household vaporizer produces a fine mist  of steam that may be used to humidify a room will be  used also Examples: 1.  Isoetharine inhalation‐ bronchial asthma 2.  Isoproterenol inhalation‐ bronchial asthma

INHALANTS A drugs or combinations of drugs the by virtue  of their high vapor pressure can be carried by a  current into the nasal passage where they exert  their effects. The device in which they bare administered  is  termed an inhaler Examples: 1.  Amyl Nitrite inhalant – treatment of anginal  pain 2.  Propylhexedrine inhalant – nasal decongestant

SYRUPS Syrups are concentrated solutions of sugar (such  as sucrose) in water or other aqueous liquids with  or without added flavoring agents and medicinal  substances 3 Types of syrups 1.  Simple syrup – concentrated solution of sucrose in  purified water alone. 2.  Medicated syrup – aqueous solution of sucrose  containing other substances as polyols(glycerin  and sorbitol) 3.  Non‐medicated/Flavored syrup – contained various  aromatic and pleasantly flavored substances and  is intended as a vehicle or flavor for preparations.

Classification of syrups A. Medicinal Classification 1. Non‐medicated/Flavoring syrups – are used as  vehicles and have no official formulas  and  therefore no detailed descriptions of the product  are found in compedia. B. Pharmaceutical Classification Based on their basic formula 1. sugar based syrups – syrups which are  concentrated solutions 2. artificial sweeteners and non‐nutritive syrups – formulated with artificial sweetening agents and  viscosity builders

Examples of Flavoring Syrups 1.  Orange Syrup ‐ This sucrose ‐ based syrup utilizes sweet orange  peel tincture, and citric acid as the source of flavor and tartness. Syrupus Aurantii, syrup of orange peel, sweet orange peel 50  mL;citric acid 5 g; talc 15 g; sucrose 820 g; purified water q.s to  make 1000 mL 2.  Ora ‐ Sweet and Ora‐Sweet SF ‐Commercially available vehicles  for the extemporaneous compounding of Syrups. Ora sweet SF  syrup is sugar free. 3.Raspberry Syrup ‐ A sucrose ‐ based syrup containing about 48%  by volume of raspberry juice 4.  Glycyrrhiza Syrup ‐ Licorice syrup, Glycyrrhiza fluid extract 250  mL; Fennel oil 0.55 mL; Anise oil 0.5 mL; syrups, q.s to make 1000  mL

5.  Cocoa Syrup ‐ Syrupus cacao, Cacao syrup, chocolate flavored,  cocoa 180 g; sucrose 600 g; liquid glucose 180 g; glycerin 50 mL;  Sodium chloride 2 g; Vanilla 0.2 g; Sodium benzoate 1 g; water q.s.  to make 1000 mL 6.Cherry Syrup ‐ Syrupus Gerasi ‐ Cherry juice 475 mL; sucrose 800  g; alcohol 20 mL; water q.s. to make 1000 mL 7.  Acacia Syrup ‐ Syrupus acaciae ‐ Acacia powder 100g; Sodium  benzoate 1 g; Vanilla tincture 5 mL; Sucrose 800 g; Purified water  q.s to make 1000 mL. 8.  Citric acid Syrup ‐ Syrupus Acidi Citrici, Syrup  lemon ‐ Lemon tincture 10 mL; Citric acid 10 g: Purified water q.s to  make 1000 mL 9.  Simple Syrup ‐ This is an 85% of sucrose in  purified  water.  This simple syrup may be used  as the basis for the  preparation of flavored or  medicated syrup.

2.  Medicated Syrups ‐ contain ingredients giving  them  therapeutic value Example: Ephedrine Sulfate Syrup ‐(for cough) ‐ Ephedrine  sulfate 4 g; Citric acid 1 g;Amaranth solution 4 mL; Caramel 0.4 g;  Lemon oil 0.125 mL; orange oil 0.25 mL; Benzaldehyde 0.06 mL;  Vanillin 0.016 g; alcohol 25 mL; Sucrose 800 g; Purified water, q.s to  make 1000 mL Ipecac Syrup ‐ emetic Note: Some syrup are use as Cathartic, Cholinergic, Decongestant,  Expectorant, Fecal Softener,  Sedative and others Examples Of Medicated Syrups By Category 1.  Analgesic Meperidine HCl Syrup ‐ Demerol Syrup 2.  Anticholinergics Dicyclomine HCl Syrup ‐ Bentyl Syrup Oxybutynin Chloride ‐ Ditropan syrup

3.  Antiemetics Chlorpromazine HCl Syrup ‐ Thorazine Syrup Dimenhydrinate Syrup ‐ Childrens Dramamine Liquid Prochlorperazine Edisylate ‐ Compazine Syrup Promethazine HCl ‐ Phenergan Syrup 4.  Anticonvulsant Sodium Valproate Syrup ‐ Depakene Syrup 5.  Antipsychotic Lithium Citrate ‐ Lithium Citrate Syrup 6.  Antihistamines Chlorpheniramine Maleate ‐ Chlor‐Trimeton Cyproheptadine HCl ‐ Periactin Syrup Hydroxyzine HCl ‐ Atarax Syrup

7.  Antitussives Dextromethorphan ‐ Benylin Syrup Diphenhydramine ‐ Benelyn Allergy Liquid 8.  Antiviral Amantadine HCl ‐ Symmetrel Syrup 9.  Bronchodilators Albuterol Sulfate ‐ Proventil, Ventolin Syrup Metaproterenol Sulfate ‐ Alupent syrup 10.  Cathartic Lactulose ‐ Chronulac Syrup 11.  Cholinergic Pyridostigmine Bromide Syrup ‐ Mestinon Syrup

12.  Decongestant Pseudoephedrine Hydrochloride ‐Children’s Sudafed Liquid 13.  Expectorant  Guaifenesin Syrup ‐ Guaifenesin Syrup 14.  Fecal Softener Docusate Sodium ‐ Colace syrup 15.  Gastrointestinal stimulant Metoclopramide Syrup ‐ Amicar Syrup 16.  Hemostatic Aminocaproic Acid ‐ Amicar Syrup 17.  Hypnotic/Sedative Chloral Hydrate ‐ Chloral Hydrate Syrup

Example Of Non Sugar Based Medicated Syrup 1. Antihistamine Chlorpheniramine Maleate

0.4 g

Glycerin

25.0 mL

Syrup

83.0 mL

Sorbitol Solution

282.0 mL

Sodium Benzoate Alcohol Color and Flavor Purified water, to make

1.0 g 60.0 mL q.s 1000.0 mL

Example Of Non Sugar Based Medicated Syrup 2. Ferrous Sulfate Ferrous Sulfate Citric acid Sorbitol Solution Glycerin Sodium Benzoate Flavor Purified water, to make

135.0 g 12.0 g 350.0 mL 50.0 mL 1.0 g q.s 1000.0 mL

Example Of Non Sugar Base Medicated Syrup 3. Cough and Cold Syrup Dextromethorphan HCL Guaifenesin

2.0 g 10.0 g

Chlorpheniramine Maleate

0.2 g

Phenylephrine HCl

1.0 g

Sodium Benzoate

1.0 g

Saccharin Sodium

1.9 g

Citric acid

1.0 g

Sodium Chloride

5.2 g

Alcohol

50.0 mL

Sorbitol Solution

324.0 mL

Syrup

132.0 mL

Liquid Glucose

44.0 mL

Glycerin

50.0 mL

Color/Flavor

q.s

Purified Water to make

1000.0 mL

Example Of Non Sugar Base Medicated Syrups 4. Acetaminophen Syrup Acetaminophen

24.0 g

Benzoic Acid

1.0 g

Disodium Calcium EDTA

1.0 g

Propylene glycol

150.0 mL

Alcohol

150.0 mL

Saccharin Sodium

1.8 g

Purified water

200.0 mL

Flavor

q.s

Sorbitol Solution, to make

1000.0mL

Components Of Syrups 1. Sugar - usually sucrose and other substitutes for sweetness and viscosity 2. Antimicrobial preservatives 3. Flavorants 4. Colorants 5. Miscellaneous - special solvents, solubilizing agents, thickeners or stabilizers

Pharmaceutical Classification based on  their basic formula 1.  Sugar Based syrups – sucrose and dextrose are  usually employed in the preparation of syrups 2. Artificial sweeteners – sugar‐free syrups which are  intended as substitute for sugar‐based syrups and  are intended to be administerd to persons who  must regulate their sugar/calorie intake.

Preservation and Storage of Syrups Generally, syrups are stored at room temperature  in tightly closed bottle and well‐filled bottles. Antimicrobial Preservatives The amount of preservatives required in a syrup  varies with the proportions of water available for  microbial growth. Among the preservatives 1.  Benzoic acid‐0.1% to 0.2% 2.  Sodium benzoate – 0.1 to 0.2% 3.  Combination of methyl, propyl, butyl parabens  totaling 0.1%

DEXTROSE Dextrose may be used as a substitute for sucrose in syrups  containing strong acids in order to eliminate the  discoloration associated with caramelization. Example: Hydroiodic syrup The difficulty or problem with dextrose are as  follows: 1.  It forms a saturated solutions in water at 70%w/v  which is less viscous than simple syrup. 2.  Dextrose dissolves more slowly 3.  Dextrose is less sweet 4.  Saturated solution supports growth of microorganism  and therefore more easily fermented.

DEXTROSE So with the use of dextrose, it is necessary to improve the  keeping qualities by adding: 1.  Preservatives which may be glycerin in 30 to 45%  which is also serves to increase viscosity. 2.  Sweeteners 3.  However, glycerin tends to develop a butyric odor or  aging Flavorants for syrup Most syrups flavored with synthetic flavorants or  with naturally occurring materials as volatile oil,  vanillin, and others, to render the syrup pleasant  tasting. Since syrups are aqueous preparations, these  flavorants must be possess sufficient water solubility

Colorants for Syrup To enhance appeal of the syrup, a coloring agent is  generally used which correlates with the flavorant  employed. The colorant used is generally water‐soluble,  non‐reactive with other components, and color stable  at the pH range and under intensity of light that the  syrup is likely to encounter during its shelf life.

Sweeteners • Non‐nutritive, synthetic sweetening agents required in the  formulation • Saccharin sodium is 300 ‐ 550 time as sweet as sucrose. It may  be used in concentration of 0.1 to 0.2% but characterized by a  bitter after taste. • Aspartylphenylalanine methyl ester is a potential low calories – 160 times sweeter than sucrose in aqueous solution.

Sweeteners and Viscosity Builders‐Sorbitol Based Syrup Sorbitol, A hexahydric alcohol, C6H14O6, made by hydrogenation of glucose is used mostly in the 70% aqueous solution USP trademark “Sorbo” Characteristics of Sorbitol 1.  Sorbitol solution is not irritating to the membrane of the  mouth and the throat 2.  Unlike sucrose, it does not contribute to the formation of  dental caries 3.  Although it is metabolized and converted into glucose it  is not absorbed from the GIT as rapid as sugars, so no  significant hyperglycemia is formed

4.  Although it is 60% as sweet as sucrose and half as  viscous as simple syrup, it has excellent “mouth feel” and  lacks acrid characteristics. 5.  Sorbitol is compatible with other polyol and simple  syrup 6.  Sorbitol is chemically stable and practically inert. 7.  Sorbitol inhibits the sticking and locking of bottle caps  which occurs with high concentration of sucrose so they  are usually combined 8.  Many drugs are more stable in sorbitol than in sucrose  solution thus may have extended shelf‐life 9.  As much as 10% v/v of alcohol can be added before  crystallization is observed same as sucrose.

Uses Of Syrups 1.  Due to sweetness, can mask the taste of salty and bitter drugs and therefore serve as pleasant tasting vehicle 2.  Used as vehicle for pediatric use due to  to their high viscosity and the  “smoothness” and mouth feel qualities. 3.  Due to the wide variety of flavors of  syrups such as orange, lemon, peppermint,  these are widely acceptable.

Preparation Of Syrups Syrups are most frequently prepared by any one  of the four methods depending upon the physical and  chemical characteristics of the ingredients. 1.  Solution of the ingredients with the aid of heat 2.  Solution of the ingredients by agitation without the  use of heat or the simple admixture of liquid  components  3.  Addition of sucrose to a prepared medicated liquid  or to a flavored liquid 4.  By percolation of either the sucrose of the  medicating substance or of the sucrose.

1. Solution of ingredients with the aid of heat Syrups are prepared by this method for the following reasons: A. When desired to prepare the syrup as quickly as possible B. When the syrups components are not damaged or volatilized by heat Procedure 1. Add the sugar to the purified water and heat until solution is affected. 2. Heat stable components are added to the hot syrup 3. Cool and made up to volume. 4. If other components are heat labile, they are added after cooling like alcohol and oil. Caution: Do not apply excessive heat - inversion of sucrose causing discoloration due to caramelization Examples : Acacia syrup, NF; Cocoa Syrup, NF; Syrup USP (85% sugar, made by cold and hot process, percolation)

2. Solution of ingredients by agitation without the aid of heat To avoid heat-induced inversion of sucrose, a syrup maybe prepared without heat by agitation Procedure: 1. Sucrose and other formulative agents maybe dissolved in purified water. 2. Place the ingredients in a bottle of greater capacity than the volume of syrup. 3. Agitate the mixture Examples: Ferrous Sulfate Syrup, Ephedrine Sulfate, Citric acid Syrup, and Glycyrrhiza Syrup

3. Percolation In this method, either sucrose maybe percolated to prepare the syrup or the sucrose of the medicinal component may be percolated to form an extractive to which sucrose or syrup may be added Procedure: 1. Purified water or aqueous solution of a medicating or flavoring liquid is allowed to pass slowly through a column of crystalline sucrose to dissolve it.

2. The percolate is collected and returned to the percolator as required until all of the sucrose has been dissolved. 3. Percolator with a pledget of cotton at the bottom is used Example: Tolu Balsam syrup - flavor for cough syrup 4. Addition of Sucrose to a Medicated liquid or to a Flavored liquid Occasionally, a medicated liquid, as a tincture of fluidextract is employed as the source of medication in the preparation of a syrup. Many such tinctures and fluidextract contain alcoholsoluble constituents and are prepared with alcoholic vehicles.

Examples: Senna Syrup, NF and Cherry Syrup

HONEY • Honey is also called “Clarified honey” or “Strained  Honey” • Honey instead of syrup was used as a base for thick  liquid preparation known as Honeys or Mels. • Honey is the secretion deposited in the honeycomb of  the bee and consists of a mixture of invert sugar – 62‐ 83%; sucrose – 8%; dextrin – 0.2% Examples: Oxymel (acid honey) – contains acetic acid – 150  mL; Purified water 150 mL; honey q.s to make 1000 mL Squill Oxymel = squill, water, acetic acid and honey

MUCILAGES • Are thick, viscid, adhesive liquids, produced by  dispersing gum in water or by extracting with  water mucilagenous principle from vegetable  substances. • Mucilages are used primarily to aid in suspending  insoluble substances in liquids due to their 1. colloidal character 2. viscosity which prevents the  immediate sedimentation

Example: Preparation: Acacia Mucilage NF Synonym: Mucilago Acaciae; Mucilage of Gum Arabic Formula : Acacia, in small fragments Benzoic acid Purified water, q.s to make

350 g 2g 1000 mL

Method: Place acacia in wide mouth graduated bottle with capacity not exceeding 1000 mL. Wash the drug with cold water, drain and add sufficient quantity of purified water in which benzoic acid has been dissolved to make 1000 mL, Stopper and lay the bottle, rotate occasionally, and when acacia has been dissolved, strain the mucilage Uses: Demulcent, suspending agent, excipient in making pills and troches,and as emulsifying agent for cod liver oil

Example: Preparation: Tragacanth Mucilage NF Synonym: Mucilago Tragacanthae Formula : Tragacanth

6.0 g

Benzoic acid

0.2 g

Glycerin

18.0 g

Purified water, q.s to make 100 g Method : Mix 75 mL of purified water with glycerin in a tared vessel, heat to boiling, discontinue application of heat, add Tragacanth and the Benzoic acid and macerate during 24 hours, stirring occasionally. Add sufficient quantity of purified water to make the mucilage 100 g, stir actively until uniform consistency and strain through muslin cloth Uses: excipient for pills or troches, suspending agent for insoluble substances for internal mixtures and as protective agent

ELIXIRS Are clear, pleasantly flavored, sweetened hdyroalcoholic  liquids intended for oral as compared to syrup, elixirs are  less sweet and viscous since they contain a lower portion of  sugar and consequently less effective in masking the taste  of medicinal substances

Advantages of elixirs 1.  Because of their hydroalcoholic character, elixirs are better  able than the aqueous syrups to maintain both water  soluble and alcohol soluble components in the solutions 2.  More preferred than syrups due to the stability character 3.  Easy to prepare which is by simple solution 4.  Pleasant flavor

Characteristics of Elixir 1.  The main ingredient  of elixirs are ethanol and water but  glycerin sorbitol, propylene glycol, flavoring agents,  preservatives and syrups are often used in preparation of  the final product 2.  The alcohol content vary from 3 to 41% depending on the  water alcohol solubility of the ingredients 3.  Although many elixirs are sweetened with sucrose, some  utilize sorbitol, glycerin, and artificial sweeteners such as  saccharin for this purpose. 4.  Elixirs having a high alcoholic content usually use as artificial  sweeteners as saccharin which is used in small quantities  only.

Preparation of Elixirs 1.  Simple solution with agitation 2.  By the admixture of two or more liquid ingredients

Classes of Elixirs 1.  Non‐medicated ‐ used in the extemporaneous filling of  prescriptions involving 1. The addition of a therapeutic agent to a pleasant tasting  vehicle 2. The dilution of an existing medicated elixir NOTE: There should be no incompatibilities between the  above and the component of the formula Example: Aromatic elixirs, Compound Benzaldehyde Elixir, Iso ‐ alcoholic Elixir 2. Medicated Elixirs – are employed for the therapeutic benefit of  the medicinal agent present. Example: 1. Phenobarbital elixir= Phenobarbital 4g; Orange oil 0.25mL;  Propylene Glycol 100mL; Alcohol 200mL; Sorbitol Solution 600m;  Color q.s purified water to make 1000mL.

The official and commercial elixirs contain a single   therapeutic agent except : Terpene hydrate and Codein Elixir The advantage of Single therapeutic agent:  Dosage taken  may be increased or decreased by taking more or less of the  elixir without much problem.  Examples: Antihistamine Elixir; Hypnotic and Sedative Elixirs  (Barbital) 2. Theophylline Elixir: Theophylline 5.3g; Citric Acid 10g; Liquid  Glucose 44g; Syrup 132.0mL; Glycerin 50mL; Sorbitol Solution  324mL; yellow No. 5 0.1g; purified water to make 100mL 3. Diphenhydramine Hydrochloride Elixir: Diphenhydramine HCl  2.5g; Orange oil 0.24mL; Cinnamon oil 0.11mL; Clove oil  0.08mL; Coriander oil 0.03mL;  Anethole 0.03mlL; Amaranth  solution 1.6 mL; alcohol 350 mL; Purified water, q.s to make  1000 mL

Example Formulations for some non‐medicated elixirs 1.  Aromatic elixir: Compound Orange spirit 12mL;  Syrup 375mL; Talc 30g; Alcohol and purified water  to make 1000mL 2.  Compound Benzaldehayde Elixir: Benzaldehyde  0.5mL; Syrup 400mL; Purified water, q.s to make  1000mL 3.  Iso‐alcoholic elixir contains low and high alcoholic 1. Low alcoholic‐ Compound orange spirit 10mL;  Alcohol 100mL; Glycerin 200mL; Sucrose  320mL; Purified water q.s to make 1000mL 2. High Alcoholic‐ Compound orange spirit 4mL;  Saccharin 3g; Glycerin 200mL; Alcohol, q.s to  make 1000mL

Examples of medicated Elixirs by Category 1.  Adrenocortical steroid Dexamethasone Elixir‐ Decadron Elixir

2.

Analgesic/Antipyretic Acetaminophen Elixir‐ Children’s Tylenol Elixir

3.

Anticholinergic/Antispasmodic Hyscyamine Sulfate Elixir –Levsin Elixir

4.

Antiasthma Diphenhydramine HCl – Benadryl Elixir

5.

Antipsychotic Fluphenazine HCl – Fluphenazine HCl

6.

Cardiotonic Digoxin – Lanoxin Pediatric Elixir

7.

Sedative/Hypnotics Butabarbital Sodium‐ Butisol Sodium Phenobarbital – Phenobarbital Elixir

GLYCERITES Solutions of mixtures of medicinal or pharmaceutical  substances in glycerin Characteristics: 1.  Generally a minimum of 50% of glycerin is present in  glycerites 2.  Due to high concentration of glycerin and the presence of  large amount of dissolved or undissolved substances.  Glycerites are generally quite viscous with some of them  reaching a jelly like consistency 3.  Glycerites are considered to be stable preparation and are not  usually as prone to microbial contamination because it  possesses preservative properties

Examples of Glycerites 1.  Starch Glycerite – Glyceratum Amyli; starch glycerin‐ used as an  emollient; starch 100g; water 200mL;Benzoic acid 2g; Glycerin  700mL 2. Tannic acid Glycerite ‐ as an astringent Tannic acid 20g; Exsiccated Sodium sulfite 02.g and Sodium citrate  1g; Glycerin q.s to make 1000g 3. Phenol Glycerite ‐ 40mL is official in BPC diluted with Glycerin  q.s 100mL 4. Boroglycerin Glycerite – antibacterial 5. Iodine and Zinc Iodide Glycerite – Glyceritum Iodi et Zinci Iodi 6. Tragacanth Glycerite – Glyceratum Tragacanthae Storage of Glycerites Glycerites are hygroscopic, therefore, should be stored in tightly  closed containers.

MIXTURES Are aqueous liquid preparations which contains  suspended insoluble solid substances and are  intended for external use Characteristics: 1.  Should have  finely divided particles to suspend more readily  and settle out much slowly than larger particles thus  uniform dosage. 2.  The more nearly colloidal it is better as protective and  adsorbent on inflamed surfaces. 3.  Palatability associated with colloidal agents ***mixtures should have “shake well” label

EXAMPLE OF MIXTURE 1.Brown Mixture - Compound mixture of Glycyrrhiza – Glycyrrhiza extract

120 mL

Antimony Potassium Citrate

0.24 g

Paregoric

120 mL

Alcohol

30 mL

Glycerin

120 mL

Purified water q.s. to make

1000 mL.

Example of Mixture 2.Kaolin Mixture (Ka-Pek) -

for diarrhea

Kaolin

200g

Pectin

10 g

Tragacanth

5g

Benzoic acid

2g

Sodium Saccharin

1g

Glycerin

20 mL

Peppermint oil

0.75 mL

Purified water, q.s. to make

1000 mL

EXTRACTIVES Extraction involves the separation of medicinally active  portions of plant or animal tissues from the  inactive components through the use of selective  solvents Galenicals include classes of preparations knows as: 1.  Decoction 2.  Infusion 3.  Fluidextracts 4.  Tinctures 5.  Pilular (semi solid) extracts 6.  Powdered extracts

Methods of Extraction 1.  Maceration • term derived from latin word “macerare”  meaning to soak.  • Process in which the properly comminuted  drug is permitted to soak in the menstruum  and the soluble constituents are dissolved Examples: (Process M) Compound Benzoin, Sweet orange Peel  Tincture; Compound Cardamon; Tolu Balsam  Tincture

Methods of Extraction 2. Percolation – Per =“through”; Colare = “strain” The process in which the comminuted drug is extracted  of its soluble constituents by the slow passage of a  suitable solvent through a column of drug. The drug is packed in a special extraction apparatus  termed as percolator with the extractive collected called  the percolate Different shapes of percolator 1. Cylindrical with little if any taper except for the lower  orifice also called Oldberg percolator 2. Cylindrical like but with a definite taper downward 3. Conical or funnel shape

The choice of type of Percolator depends upon 1. Nature of the drug 2. Type of product prepared 3. Quantity of drug to be extracted Processes and steps of Percolation 1. Preparation of the dried crude drug for percolation a. Powdering b. Moistening 2. Packing the percolator 3. Period of Maceration 4. Percolation and collection of percolate 5. Adjustment of concentration of percolation as required

The rates of flow 1. Percolate slowly – rate will not exceeding 1 mL of  percolate/minute 2. Percolate at a moderate rate ‐ rate of 1 to 3mL/minute. 3. Percolate rapidly – rate of 3 to 5 mL per minute.

Methods of Extraction 3. Digestion form of maceration with gentle heat 4. Infusion process in which vegetable drugs, generally coarsely  comminuted, are extracted of the water‐soluble constituents 5. Decoction process of boiling vegetable substances with water to  extract the soluble principles

EXTRACTS Are concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents of the respective drugs with suitable menstruum, evaporation of all or nearly all the solvents, and adjustment of the residual masses or powders to the prescribed standards. Methods of Preparation Prepared by percolation then evaporation off the solvent either by distillation under pressured and using reduced heat.

3 Forms of Extract (depending upon the extent of the removal of solvent) 1. Semiliquid extracts are those of a syrupy consistency 2. Pilular or solid extracts of a plastic consistency 3. Powdered extracts prepared to be dry by the removal of all the solvent Packaging and Storage of Extracts Must be packaged in wide mouth containers or plastic tubes and closely tight to prevent loss of moisture which would result in its becoming hard and unstable for use Examples: Belladonna Extract NF; Cascara Sagrada Extract NF and Pure Glycyrrhiza Extract

TINCTURES Are defined as alcoholic or hydro alcoholic solution  prepared from vegetable material or from chemical  substance.

TOPICAL SOLUTIONS AND TINCTURES Topical solutions employ an aqueous vehicle, whereas the topical tinctures characteristically employ an alcoholic vehicle. As required, co-solvents or adjuncts to enhance stability or the solubility of the solute are employed. Topical solutions and Tinctures are prepared by simple solution and self -preserved. Are usually packaged in glass bottles having an applicator tip as part of the cap assembly, or in plastic squeeze bottles which deliver the medication in drops. All medication intended for external use should be clearly labeled “FOR EXTERNAL USE ONLY” and kept out of the reach of youngsters.

Examples Of Solutions Applied Topically 1. Aluminum acetate - Aqueous vehicle Astringent (Burow’s Solution) 2. Aluminum Subacetate - Aqueous vehicle Astringent (Modified Burow’s) 3. Calcium Hydroxide - Aqueous vehicle Astringent - (Lime Water; Liquor Calcis) 4. Coal Tar - Alcoholic vehicle - Antieczematic, antipsoriatic (Liquor Carbonis Detergens: Liquor Picis carbonis; LCD) 5. Hydrogen Peroxide Topical Solution Aqueous vehicle - Anti-infective (Peroxide)

6. Chlorhexidine Gluconate Solution - for skin wound and general skin cleanser, surgical scrub, and preoperative skin preparation, effective in gram negative and positive such as Pseudomonas aeruginosa 7. Povidone-Iodine - Aqueous vehicle - Anti-infective (Betadine Solution) 8. Thimerosal - Aqueous vehicle - Antibacterial and mild fungistatic (Merthiolate Solution) Examples Of Tinctures Applied Topically

1. Green soap Tincture - Alcohol vehicle - Detergent. Also contains 2% lavender oil as perfume 2. Iodine Tincture - Alcohol - water vehicle - Antiinfective 3. Compound Benzoin Tincture - alcohol - Topical protectant

Variations of Official Tinctures are on: 1.  Method of Preparation 2.  Strength of their active constituent 3.  Alcohol content 4.  Intended use in medicine or pharmacy

Method of Preparation of Tinctures 1.  By simple solution ‐ tinctures prepared from  chemical substances. Example: Iodine, Thimerosal,  Nitromersol  green soap tinctures 2.  By extraction ‐ by maceration or percolation Examples: Compound Cardamon  Tincture

Preparation of Tinctures 1. Maceration Examples: Compound Benzoin Tinctures; Sweet Orange  Peel Tincture and ToLu Balsam Tincture 2. Percolation Examples: Belladona Tincture and Vanilla Tincture

Strength of their Active components • There is no set strength for compound tincture. They vary  with particular preparation. • The amount of crude drugs used to prepare each 100mL of  tincture is generally as follows: (Belladona Tincture) • Potent drugs: Balledona leaf –10 g • Non potent drug: Tolu Balsam – 20 g • Undried fresh fruit peel: sweet orange  peel – 50 g

Alcohol Content Tinctures are considered to be stable preparation containing alcohol to protect against microbial growth. Green soap Tincture - 28 to 32% alcohol Tolu Balsam Tincture - 77 to 83% alcohol Pharmaceutical Uses As flavoring tinctures like vanilla, sweet orange peel, Tolu balsam tinctures. Medicinal use - Iodine Tincture, Thimerosal, Nitromersol Tinctures - Anti-infective; Compound Benzoin Tincture - Topical protectant; Green soap Tincture - Topical detergent; Paregoric Tincture - Antiperistalsis; Belladona Tincture - Anticholinergic

Disadvantages of Tinctures 1. Unpleasant tasting 2. Physician will prefer single drug instead of preparation  from plants 3. High alcohol content

FLUIDEXTRACT Are liquid preparations of vegetable drugs containing  alcohol as a solvent or as a preservative or both, and so  made that each mL contains the therapeutic  constituents of 1g of the standard drug that it  represents

Characteristics of Fluidextract 1. Because they contain alcohol and are highly  concentrated, fluidextracts are sometimes referred to  as “100% tinctures”  2. Fluidextracts of potent drugs are ten times as  concentrated or as potent as corresponding tincture Example: Belladonna Tincture is 0.6mL while its  fluidextract is 0.06mL Disadvantages of Fluidextract 1. Because of their concentrated nature, many  fluidextracts are considered too potent for safe self  administration 2. Too bitter tasting or otherwise unpalatable

Preparations of Fluidextracts • Percolation is preferred in all cases because of the  exhaustive extraction required. 3 Processes labeled A, D, or B and C or E Process A -

entails exhaustive percolation with an alcoholic or hydroalcoholic menstruum. Example: Senna Fluidextract

Process B or D -

is used in the preparation of fluidextract with boiling water as the menstruum and alcohol generally added to the concentrated percolate as preservative. A heat resistant or metallic percolator is used. Example: Aromatic Cascara Sagrada

Process C and E -

is intended to facilitate total drug extraction by collecting 1000 mL of percolate from each 1000 g of drug, uses long narrow column of drug and percolation under pressure

Official Preparation 1. Glycyrrhiza Fluidextract - Licorice root Fluidextract - flavoring agent 2. Eriodictyon Fluidextract - Yerba Santa Fluidextract - cathartic 3. Cascara Sagrada Fluidextract Rhamnus Purshiana Fluidextract 4. Aromatic Cascara Sagrada Fluidextract 5. Senna Fluidextract - Fluidextratum Sennae

NASAL PREPARATIONS Are aqueous preparations rendered isotonic to nasal  fluids and stabilized and preserved as required Example of Some Nasal Preparations 1. Afrin Nasal Spray/drops‐ Oxymetazone‐ Nasal decongestant 2. Beconase AQ Nasal Spray‐ Beclomethasone diproprionate‐ synthetic corticosteroid 3. Diapid Nasal Spray – Lopressin‐ Antidiuretic, prevention of  diabetes 4. Nasalcrom spray – Cromolyn‐ allergic rhinitis

5. Ocean Mist – isotonic sodium chloride‐ restore  moisture/relieve dry inflamed nasal 6. Privine HCl solution‐ Naphazoline HCl‐ nasal adrenergic 7. Syntocinon Spray – Oxytocin ‐synthetic, preparatory to  breast feeding

8. Neo‐Syneprine – Oxymethazoline HCl‐ nasal adrenergic 9. Nasalide Nasal Solution‐ Flunisolide –parennial/seasonal  rhinitis OTIC SOLUTIONS As sometimes referred to as ear or Aural preparations  preparations frequently used in the ear, with suspensions  or ointments also finding some application. Usually placed  in the ear canal by drops or small amounts for the removal  of excessive cerumen (ear wax), or treatment of ear  infections, inflammation or pain. Examples of Some Commercial Otic Solutions 1. Americaine‐ Benzocaine – Local anesthetic

2. Auralgan‐ Antipyrine, Benzocaine – Acute Otitis Media 3. Cerumenex drops – Triethanolamine – Cerumenolytic agent;  removes impacted earwax

4. Chloromycetin – Chloramphenicol – Anti‐infective 5. Cortisporin Solution –Polymyxin B sulfate‐ antibacterial 6. Debrox Drops‐ Carbamide Peroxide – Ear wax removal  7. PediOtic ‐ Polymyxin B sulfate, neomycin sulfate ‐ Antibacterial 8.  Metreton ‐ Prednisolone sodium phosphate ‐ Antiinflammatory 9.  Otobiotic Solution ‐ Polymyxin B Sulfate, hydrocortisone ‐ Antibacterial 10.  VoSol Solution ‐ Acetic acid ‐ Antibacterial/Antifungal

DOUCHES A douche is an aqueous solutions which is directed against a part or into a cavity of the body. It functions as a cleansing or antiseptic. Characteristics Douches are usually directed to the appropriate body parts by using Bulb syringe. Example: vaginal syringe is made up of an 8 to 10 ounce capacity bulb syringe with a large vulcanite or rubber spray tube.

KINDS OF DOUCHES 1. Eye Douche - used to removed foreign particles and discharges from the eyes, is directed gently at an oblique angle and is allowed to run from the inner to outer corner of the eye. 2. Pharyngeal Douche - are used to prepare the interior of the throat for an operation and to cleanse it in suppurative conditions (formation of discharge of pus). 3. Nasal Douche - used to cleanse nasal passage 4. Vaginal Douche - used for irrigative cleansing of the vagina therefore for hygienic effects, also called urethral douche or irrigation

Characteristics Douches are more frequently dispensed in the form of powder with directions for dissolving in a specified quantity of water, usually warm Dobell’s Solution Tablets (Compound Sodium Borate Solution NF) used for nasal or pharyngeal douches. Douches are not official as a class of preparations but general substances in the USP and NF are frequently employed as such in weak solution. Example: Benzalkonium Chloride used in various douches

ENEMAS Enemas are also known as CLYSTER, they are rectal injections employed to: 1. Evacuate the bowel 2. To influence the general system by absorption 3. Affect locally the seat of disease and for 4. For diagnostic visualization of GIT USES: antihelmintic, nutritive, sedative or stimulating properties or they may contain radiopaque substances for roentgenographic examination of the lower bowel

Characteristics: Enemas are usually given at body temperature in quantities of 1 to 2 pints injected slowly with enema syringe. If they are to be retained in the intestine, they should not be used in larger quantities than 6 fluid ounces for an adult.

Examples: 1. Enema of soft soap - prepared by dissolving 50 g of soft soap with purified water to make 1000 mL.

Example Preparation: Barium Sulfate Enema Synonym: Barium Salt Latin Name : Baric Sulfae Formula : Barium Sulfate Acacia Mucilage

120 g 100 mL

Starch Enema, q.s To make

500 mL

Procedure: Prepared by mixing Barium Sulfate (120 g) with 100 mLof acacia mucilage and sufficient Starch Enema to make 500 mL Starch Enema is made by triturating 30 g of powdered starch with 200 mL cold water then sufficient quantity of water added to make 1 Liter. Use: For diagnostic visualization of GIT

2 Types Of Enema 1. Evacuation Enemas - are rectal enemas employed to promote evacuation of bowel and to cleanse the colon for retention and for diagnosis. Available in disposable plastic squeeze bottles containing a pre measured amount of enema solution. The agents present are solutions of sodium phosphate, sodium biphosphate, glycerin and docusate potassium and light mineral oil.

2. Retention Enemas - a number of solutions are administered rectally for the local effects of the medication Examples: Hydrocortisone - local; aminophylline systemic effect

Types Of Retention Enema 1. Nutritive Enema - supply nutrient to the patient 2. Medicated Enema - supply medication for systemic effect 3. Disgnostic Enema - BaSO4 and Fleet Enema Other Enemas 1. Aminophylline Enema - NLT 90% and NMT 110% of C6H24N10 . 2H2O 2. Methyl Prednisolone Acetate - NLT 90% and NMT 110% of C24H32O6 3. Cortisol Enema - NLT 90% and NMT 110% of C21H30O5

Miscellaneous Preparations for Topical Application 1.

Rubbing Alcohol contains about 70% of ethyl alcohol by volume, the remainder consisting of water, denaturants with or without color additives and perfume oils, and stabilizers. Uses: employed as rubefacient externally, as a soothing rub for bedridden patients, a germicide for instrument, and skin cleanser prior to injection Synonym: Alcohol Rubbing Compound

2.

Isopropyl Rubbing Alcohol is about 70% by volume of isopropyl alcohol, the remainder consisting of water with or without color additives, stabilizers, and perfume oils. Uses: as rubefacient and soothing rub; 91% isopropyl alcohol - employed by diabetic patients in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin

Miscellaneous Preparations for Topical Application 3. Hexachlorophene Liquid Cleanser - is an antibacterial sudsing emulsion containing colloidal dispersion of hexachlorophene 3% W/W in a stable emulsion consisting of entsufon sodium (synthetic detergent), petrolatum,lanolin cholesterols, methylcellulose, polyethylene glycol, PG monostearate, lauryl myristyl diethanolamide, sodium benzoate and water Uses: bacteriostatic cleansing agent, surgical scrub

LINIMENTS Are alcoholic or oleaginous solutions or emulsions of various medicinal substances intended for external application to the skin, generally with rubbing. Formerly called “embrocations” for substance applied with rubbing.

Types Of Liniments 1. Alcoholic liniments 2. Oil 3. Dental liniments - not official

Alcoholic liniment - used as rubefacient ( induce mild irritation with reddening of the skin), counterirritant, mildly astringent, and penetrating effect. Oily liniment are milder in action and less irritating to the skin than the alcoholic, used as protective coating and use as rubefacient for muscular pain

Different Forms by which Liniments can occur 1. As a emulsion 2. As a suspension 3. As a solution Components of Liniments 1. Counterirritant

3. Local Anesthetics

2. Antiseptic

4. Analgesics

Methods of Preparation Liniments are prepared in the same manner as solutions, emulsions or suspensions All liniments Must Bear A Label Indicating 1. For external use only 2. Shake well for emulsion or suspension 3. Store in tight containers 4. Not to be applied to bruises or broken skin areas

Factors to be considered in using solvents or vehicle 1. Type of action desired, whether rubefacient, counterirritant or just massage - alcohol or oil 2. Solubility of the desired components in the various solvents. For oleaginous liniments the solvents may be fixed oil, almond oil, peanut oil, sesame oil or cotton seed oil or volatile oil such as wintergreen or turpentine oil or combination of fixed or volatile oil. NOTE: There are presently no official liniments in the USP and NF

White Liniment BPC Ammomiun chloride

12.5 g

Dil. Ammonia Solution

45.0 mL

Oleic acid

85.0 mL

Turpentine oil

250.0 mL

Water

625.0 mL

Mix oleic acid with the turpentine oil, add the diluted Ammonia mixed with 45 mL of previously warmed water. Shake. Dissolve the ammonium chloride in the remainder of the water, add to the emulsion and mix.

Calamine Liniment/Lotion. Oily BPC Calamine

50 g

Wool fat

10 g

Oleic acid

5 mL

Arachic oil

500 mL

Ca(OH)2 solution to make

1000 mL

Triturate the calamine with the wool fat, the arachis oil and oleic acid, previously melted together. Transfer to a suitable container, add the Ca(OH)2 solution and shake vigorously.

CAMPHOR LINIMENT Linimentum Camphoras; Camphorated Oil Camphor

200 g

Cottonseed oil

800 g

to make

1000 g

Place the cottonseed oil into a suitable dry flash or bottle, heat on the steam bath. Add camphor and stopper the container securely. Agitate to dissolve the camphor without further heating.